Pancreatic cancer is the fourth-leading cause of cancer death in men and fifth in women, with greater than 30,000 deaths annually in the United States. According to data from the Surveillance, Epidemiology, and End Results (SEER) database, approximately 20% of cases affect people under the age of 60, hereafter termed young-onset pancreatic cancer. The investigators propose to define the factors influencing risk for young-onset pancreatic cancer utilizing the core resource from the Pancreatic Cancer SPORE program at the Mayo Clinic. This database consists of risk-factor questionnaires, medical records, blood, and surgical specimens. From these available materials, assessments will be made regarding the impact of known and as yet unknown contributions to risk for the development of pancreatic cancer. Initial evidence from the applicant's work and the published literature is presented in this application which suggests that familial cancer syndromes, inherited forms of pancreatitis, and DNA repair abnormalities may each explain a proportion of the young-onset cases. We propose to investigate the contribution of these factors to risk for young-onset pancreatic cancer. Frequency of mutations in BRCA2, CDKN2A (Familial Melanoma), Fanconi Anemia Genes (FANCC and FANCG), CFTR, SPINK1, PRSS1, and polymorphisms of several DNA repair genes will be determined among 500 young-onset cases versus 1000 older-onset cases and 1000 healthy controls. The composition to the SPORE resource enables thorough examination of these candidate genes in the context of environmental and behavioral factors. The principal investigator, Dr. Robert McWilliams, has clinical training in medical oncology, and post-doctoral training in the genetic epidemiology of cancer. This grant will enable him to elucidate the contributors to young-onset pancreatic cancer and establish himself as an independent investigator in the genetic epidemiology of cancer. This proposed research is 100% relevant to pancreatic cancer. [unreadable] [unreadable] [unreadable]